ATP敏感性钾通道突变与新生儿糖尿病iDEND综合征

ATP敏感性钾通道(ATP-sensitive K+chan-nels,KATP)由SUR1和Kir6.2亚基组成,是葡萄糖刺激胰岛β细胞分泌胰岛素的关键部位。新生儿糖尿病iDEND综合征(intermediate developmental delay,epilepsy,and neonatal diabetes syndrome)是由KATP通

Mutation of ATP-sensitive K+ channels and neonatal diabetes iDEND syndrome

Activating mutation in the KCNJ11 gene encoding Kir6.2 subunit of adenosine triphosphate(ATP)-sensitive potassium(KATP) channel gives rise to intermediate developmental delay,epilepsy and neonatal diabetes(iDEND) syndrome,a rare hereditary endocrine metabolic disorder characterized by neonatal diabetes accompanied by developmental delay and muscle weakness,but no epilepsy.The Kir6.2 Val59→Met59(V59M) activating mutation is the common cause of iDEND syndrome(>50%).Activating mutation causes iDEND syndrome by inhibiting normal closure of ATP-sensitive K+ channel,which leads to reduce insulin secretion.Most of such patients are more sensitive to sulfonylurea.High blood-brain barrier permeability and sulfonylurea receptor 1(SUR1)-specific drugs are expected to become a major therapy.